Introduction 1 2 3 3 1 1 4 5 6 7 9 10 5 11 10 10 2+ 3+ 12 2+ 4 1 1 9 13 9 1 7 14 10 15 14 15 16 15 7 7 7 16 7 17 7 18 19 20 21 7 18 19 22 9 19 22 44 45 46 MRI assessment of tissue iron Relaxation theories 5 47 48 7 49 50 55 48 56 57 53 54 MR methodologies 19 23 26 30 58 62 30 32 34 37 39 43 58 63 SIR methods 19 23 25 27 30 58 62 19 23 25 27 30 58 61 62 58 60 19 64 39 19 T2 relaxometry methods 65 66 67 39 40 39 40 39 40 44 T2* relaxometry methods 0 −TE/T2* 0 68 35 42 68 71 35 42 68 Hybrid relaxometry methods 34 72 73 34 73 Comparison of the MRI methodologies SIR versus relaxometry 63 1 35 63 Fig. 1 a arrows b T2, T2* and hybrid methods 35 74 74 75 76 77 43 MRI studies of individual iron overloaded organs 7 15 18 78 79 79 80 19 22 44 17 18 28 39 43 58 60 62 77 81 84 28 81 82 84 Liver 2 18 23 28 32 44 68 85 18 23 32 39 40 44 68 85 18 30 58 18 23 28 32 44 68 85 77 86 18 39 77 Fig. 2 A 17-year-old male with β-thalassaemia major. Axial scan, fourth echo of a multiecho spin-echo sequence (TR/TE: 2000/20, 40, 60, 80, 100, 120, 140, 160 ms), shows low-signal intensity in the liver, bone marrow of the spinal body and the pancreas suggesting iron overload 7 18 19 28 39 40 58 61 87 28 58 39 40 7 78 88 92 88 82 93 7 Heart 94 95 22 7 3 22 28 39 40 68 82 96 98 28 39 40 68 97 88 28 39 68 Fig. 3 a arrow arrowhead b asterisk 22 37 38 68 68 22 38 40 99 100 42 101 42 28 82 Pituitary gland and brain 102 103 102 103 4 104 28 43 83 105 83 28 43 81 28 81 84 Fig. 4 a arrow asterisks 112 b arrow asterisk 106 106 Pancreas 107 108 61 84 109 109 61 84 84 5 Fig. 5 a arrow b arrow Adrenals 103 5 87 Spleen, lymph nodes and bone marrow 1 13 59 60 62 84 5 62 78 110 111 60 60 59 84 59 Conclusion It is evident that MR relaxometry has the potential to become the method of choice for non-invasive, safe and accurate assessment of iron load. Further theoretical research, along with studies monitoring wider age groups of patients are needed before a generally accepted protocol can be established. Until then, extreme caution is needed in its clinical application and interpretation. Experimental artefacts, non-optimized protocols, poor data analysis and unawareness of the inherent limitations of current methodologies in assessing a heavy body iron burden can result in misleading diagnosis and inappropriate management of thalassaemia patients with iron overload. Future experimental developments in relaxometry based on a better theoretical understanding of the contribution of the iron-containing proteins to the MR signal are expected to further strengthen its clinical role in the monitoring of patients with β-thalassaemia major.